ABSTRACT Despite the success of antiretroviral therapy (ART), individuals living with HIV experience an increased risk of coronary artery disease (CAD). Although increased arterial inflammation on 18F-FDG-PET was shown to be associated with high risk plaque features (HRPFs) in those with HIV and subclinical atherosclerosis, there is no evidence of increased arterial inflammation in optimally treated HIV-infected adults with full viral suppression, low cardiovascular risk and no known CAD when the imaging results are compared to those from HIV- uninfected controls. These findings suggest that HIV-associated atherosclerosis may be triggered by factors other than HIV-associated inflammation such as traditional cardiovascular risk factors or cocaine use. Other evidence indicates that cocaine is associated with coronary atherosclerosis. It was also shown that cocaine use modifies the effect of HIV on subclinical coronary atherosclerosis. Supported by DA035632, this research team enrolled 102 daily cocaine users (including 84 HIV-infected) with contrast-enhanced coronary CT angiography (CCTA)-confirmed significant (>50% in diameter) coronary stenosis, and employed a cash- incentive approach to systematically reinforce cocaine abstinence. The study demonstrated that continued cocaine use led to coronary plaque volume progression, while abstinent or reduced cocaine use led to plaque volume regression. However, whether cocaine use influences plaque characteristics in HIV-infected cocaine users has not been investigated. Plaque characteristics are important because rupture-prone coronary plaques might not necessarily be only those, which cause obstructive stenosis, and that HRPFs are independent of the severity of coronary artery luminal stenosis. However, identification of the strongest predictor of CAD among four HRPFs, the napkin-ring sign (NRS), at present, is based only on expert subjective opinion. A landmark cardiovascular radiomics study calculated 4,440 radiomic features for each coronary plaque and identified a subset of these parameters which predicted NRS, a qualitative feature of prognostic imaging marker of acute coronary syndrome. It is quite possible that with the cardiac radiomic approach, the association between cocaine use and this critical biomarker will be further clarified. The objective of the proposed study is to examine whether cocaine use influences plaque features in HIV-infected cocaine users. The proposed study will perform radiomic analyses on the imaging data from 102 participants on DA035632. The specific aims of this study are: (1) To examine whether continued cocaine use is associated with the NRS and its associated radiomic features in HIV-infected cocaine users with significant coronary plaques, (2) To examine whether abstinent or reduced cocaine use ameliorated NRS and its associated radiomic features in HIV-infected cocaine users with significant coronary plaques, (3) To compare NRS and its associated radiomic features between HIV infected and uninfected participants, and (4) To validate the findings generated from this study.